Much attention has been directed in recent years to biological functions of oligosaccharides as the third biogenic polymers in the living body following nucleic acids and proteins. It has been found that the oligosaccharides present on the surfaces of cells have a wide variety of functions such as intercellular transmission of information and interaction between the oligosaccharide and an internal matrix such as virus. It is an urgent problem to clarify the structure-activity relationship for understanding many of biological processes involving oligosaccharides. However, naturally occurring oligosaccharide compounds possess microheterogeneity in structure in terms of branching, stereochemistry, and molecular weight, and chemically pure oligosaccharides are extremely difficult to separate from living body samples by purification procedures. In view of such problems, it is strongly desired to provide by chemical synthesis chemically pure oligosaccharide compounds having a clarified structure.
The 1,2-transglycoside linkage is a typical glycoside linkage which is generally found in oligosaccharides. The conventional method of preparing this glycoside bond stereoselectively uses 2-acyl protected glycosides as glycosyl donors, and the acyl group serves as stereodirecting group for the stereoselective formation of 1,2-trans glycosides by intramolecular participation. However, this process always has the problem of giving an ortho ester as a by-product.
The present inventor developed an iterative glycosylation reaction for preparing oligosaccharides by repeating the same reaction with use of thioglycoside only (Nonpatent Literature 1). This method was very effective for saccharide derivatives having an amino group at the 2-position, such as glucosamine, whereas it was not effective for other selective formation of ortho ester in the case where a saccharide derivative having a hydroxyl group at the 2-position, such as glucose, galactose or the like, was used.
wherein Ph is phenyl, and Bn is benzyl.[Nonpatent Literature 1] Angew Chem. Int. Ed. 2004, 43, 2145.
An object of the present invention is to provide a process for selectively preparing a 1,2-transglycoside compound by inhibiting the formation of an o-ester by-product in saccharide derivatives having a hydroxyl group at the 2-position.